RNA-seq analysis revealed that the cardiotoxicity caused by herceptin is due to the release of PTX3.
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE200325 | GEO | 2022/12/01
REPOSITORIES: GEO
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Project description:RNA-seq analysis revealed that the cardiotoxicity caused by herceptin is due to the release of PTX3.
| PRJNA824071 | ENA
Project description:The human long pentraxin PTX3 has complex regulatory roles at the crossroad of innate immunity, inflammation, and tissue repair. PTX3 can be produced by various cell types, including vascular endothelial cells (ECs), in response to pro-inflammatory cytokines or bacterial molecules. But PTX3 has also been involved in the regulation of cardiovascular biology, even if contrasting results have been so far provided in both preclinical and clinical research. Therefore, we compared the proteomic profiles of human ECs isolated from umbilical cords (Human Umbilical Vein ECs, HUVECs), and we identified 19 proteins more abundant in the proteome of control ECs and 23 proteins more expressed in PTX3 silenced cells.
2023-03-11 | PXD036691 | Pride
Project description:Trastuzumab is a monoclonal targeted therapy widely used to treat human epidermal growth factor receptor 2 (HER2+) over expressed breast cancer which confers an aggressive cancer type and comprises ~25% of breast cancer. Trastuzumab yields improved breast cancer related outcomes, but survival benefits are in part offset by cardiotoxicity - as evidenced by 10-15% of patients develop cardiomyopathy and 2-4% develop congestive heart failure. Approximately 20-30% of patients have either temporary or permanent discontinuation of trastuzumab therapy due to its cardiotoxicity, raising concern for inadequate cancer treatment and recurrence. Current screening strategies for trastuzumab-induced cardiotoxicity rely on non-invasive imaging such as echocardiography, but conventional imaging techniques provide limited a priori risk stratification for cardiotoxicity. We have utilized patient-specific iPSC-CMs derived from HER2+ breast cancer patients with and without evidence of TIC as a model to better elucidate the mechanisms of Trastuzumab-indued cardiotoxicity.
2024-06-05 | GSE264120 | GEO
Project description:PTX3, as the long member of the pentraxin family, is produced mainly by dendritic cells, macrophages, and endothelial cells in response to inflammation. Growing amount of studies suggest that PTX3 can exert potential contradictory roles in inflammation regulation, antimicrobial resistance, and disease pathogenesis, depending on the tissue context, cellular source, and levels of production. To characterize the potential involvement of PTX3 in macrophage function, transcriptome sequencing (RNA-seq) was performed in human THP1-derived macrophages with PTX3 depletion. Notably,genes enrichment in PI3K/AKT signaling , JAK/STAT signaling and autophagy pathway were observed in PTX3 deficiency macrophages. This study highlights the critical roles of PTX3 on regulation macrophages homeostasis.
2023-10-01 | GSE192726 | GEO
Project description:PTX3 is an essential component of humoral innate immunity, involved in resistance to selected pathogens and in the regulation of inflammation1-3. The present study was designed to assess the presence and significance of PTX3 in COVID-194-7. RNA-seq analysis of peripheral blood mononuclear cells, single-cell bioinformatics analysis and immunohistochemistry of lung autopsy samples revealed that myelomonocytic cells and endothelial cells express high levels of PTX3 in COVID-19 patients. Increased plasma concentrations of PTX3 were detected in 96 COVID-19 patients. PTX3 emerged as a strong independent predictor of 28-day mortality in multivariable analysis, better than conventional markers of inflammation, in hospitalized COVID-19 patients. The prognostic significance of PTX3 abundance for mortality was confirmed in a second independent cohort (54 patients). Thus, circulating and lung myelomonocytic cells and endothelial cells are a major source of PTX3, and PTX3 plasma concentration can serve as an independent strong prognostic indicator of short-term mortality in COVID-19.
2020-10-29 | GSE160351 | GEO
Project description:The use of tubulin binders (TBs) in oncology indications often is associated with cardiotoxicity, the mechanism of which has not been elucidated. We observed that a single administration of TBs to rats caused an increase in the number of mitotic figures in the myocardial interstitium after 24 hours. We therefore hypothesized that interstitial cells are the primary target of TBs. To test this hypothesis, we evaluated the acute effects of a single intravenous administration of 3 reference TBs, colchicine (0.2 and 2 mg/kg), vinblastine (0.5 and 3 mg/kg), and vincristine (0.1 and 1 mg/kg) 6 and 24 hours after dosing. Mitotic arrest was identified at 24 hours in all high-dose groups based on an increase in the number of mitotic figures in the interstitium coupled with a dramatic decrease in the number of Ki67-positive interstitial cells. Analysis of the myocardial transcriptomic data further supported G2/M cell cycle arrest 6 hours after dosing with the high-dose groups of all 3 compounds. Apoptotic figures and an increase in the number of cleaved caspase 3-positive cells were identified at 6 and 24 hours at the highest dose of each compound almost exclusively in interstitial cells; a few cardiomyocytes were affected as well. Transcriptomic data further suggested that some of the affected interstitial cells were endothelial cells based on the up-regulation of genes typically associated with vascular damage and down-regulation of Endothelial Cell-Specific Molecule 1 and Apelin. Taken together, these data identify endothelial cells of the myocardium as the primary target of the cardiotoxicity of TBs and identify cell cycle arrest as the mechanism of this toxicity. Gene expression was profiled in the myocardium of rats at 6 and 24 hr after a single dose of colchicine, vinblastine or vincristine.
2010-01-01 | E-GEOD-19290 | biostudies-arrayexpress
Project description:We aimed to investigate the effect of PTX3 on macrophages functions. After PTX3 stimulation for 18 h in THP-1 macrophages, total RNA were harvested for RNA-seq analysis of ctrl (n = 1) and PTX3 group (n = 1).
2023-03-20 | GSE227402 | GEO
Project description:These data can be used for evaluation of the clinical utility of the research-based PAM50 subtype predictor in predicting pathological complete response (pCR) and event-free survival (EFS) in women enrolled in the NeOAdjuvant Herceptin (NOAH) trial. The NeOAdjuvant Herceptin [NOAH] trial demonstrated that trastuzumab significantly improves pCR rates and 3-year event-free survival (EFS) in combination with neoadjuvant chemotherapy compared with neoadjuvant chemotherapy alone in patients with HER2+ breast cancer.
2014-01-21 | GSE50948 | GEO
Project description:The use of tubulin binders (TBs) in oncology indications often is associated with cardiotoxicity, the mechanism of which has not been elucidated. We observed that a single administration of TBs to rats caused an increase in the number of mitotic figures in the myocardial interstitium after 24 hours. We therefore hypothesized that interstitial cells are the primary target of TBs. To test this hypothesis, we evaluated the acute effects of a single intravenous administration of 3 reference TBs, colchicine (0.2 and 2 mg/kg), vinblastine (0.5 and 3 mg/kg), and vincristine (0.1 and 1 mg/kg) 6 and 24 hours after dosing. Mitotic arrest was identified at 24 hours in all high-dose groups based on an increase in the number of mitotic figures in the interstitium coupled with a dramatic decrease in the number of Ki67-positive interstitial cells. Analysis of the myocardial transcriptomic data further supported G2/M cell cycle arrest 6 hours after dosing with the high-dose groups of all 3 compounds. Apoptotic figures and an increase in the number of cleaved caspase 3-positive cells were identified at 6 and 24 hours at the highest dose of each compound almost exclusively in interstitial cells; a few cardiomyocytes were affected as well. Transcriptomic data further suggested that some of the affected interstitial cells were endothelial cells based on the up-regulation of genes typically associated with vascular damage and down-regulation of Endothelial Cell-Specific Molecule 1 and Apelin. Taken together, these data identify endothelial cells of the myocardium as the primary target of the cardiotoxicity of TBs and identify cell cycle arrest as the mechanism of this toxicity.
2010-01-01 | GSE19290 | GEO
Project description:The pattern recognition receptor long pentraxin-3 (PTX3) plays conflicting roles in cancer by acting as an oncosuppressor or as a pro-tumor mediator depending on tumor context. Triple negative breast cancer (TNBC) represents the most aggressive histotype of breast cancer, characterized by the lack of efficacious therapeutic targets/approaches and poor prognosis. In this study, in silico data and experimental evidences indicate that PTX3 is produced by tumor parenchyma in TNBC and that its expression levels correlate with tumor stage. On this basis, the impact of PTX3 silencing or its overexpression on the tumorigenic potential of TNBC cell lines was analyzed. Gene expression and in vitro results demonstrate that high levels of PTX3 expression confer a high aggressive/proliferative phenotype, fosters stem-like features, and rewires the energy metabolism in TNBC cells. This results in a more tumorigenic potential in vivo when TNBC cells are grafted in immune-compromised and syngeneic animals. Mechanistically, our data reveal a strong positive correlation between PTX3 expression and the antitumor activity of Toll-like receptor 4 (TLR4) inhibition in TBNC, demonstrating for the first time that PTX3-driven TNBC aggressiveness is due to PTX3-mediated activation of TLR4 signaling. Altogether, these data shed light on the role of tumor-produced PTX3 in TNBC and uncover the importance of the PTX3/TLR4 pathway for therapeutic and prognostic exploitation in TNBC.
2021-11-06 | GSE188315 | GEO